Redox-mapping MRI in rodent brain with nitroxide contrast agents

INTRODUCTION Overproduction of reactive oxygen species (ROS) and decreased antioxidant defense system may contribute to numerous brain disorders such as stroke, epilepsy, Parkinson’s disease, and Alzheimer’s disease. Non-invasive evaluation and visualization of oxidative stress is important to elucidate the role of ROS in brain diseases. In order to visualize the effect of ROS in vivo, nitroxide compounds have been used as redox-sensitive contrast agents in EPR imaging, and recently these compounds have also been started to be used as a redox-sensitive T1 contrast agents in MRI [1,2]. Paramagnetic nitroxide works as an MRI contrast agent, but not when reduced to its hydroxylamine derivatives. Therefore the ratio of paramagnetic nitroxide / diamagnetic hydroxylamine has been shown to be dependent on the redox state of the tissues. With this, MRI can show the mapping image of the redox status of the animal disease models being examined. The purpose of this study was to examine the possibility and ability of nitroxide compounds with different lipophilicities as a redox-mapping tool in MRI of brain disease animal models such as epilepsy and transient cerebral ischemia. The results were discussed with reference to the data obtained by EPR spectrometry.